As a model for understanding RNA-protein interactions we are studying the structure of the Rev-Response Element RNA in complex with peptides derived from the Rev protein. Rev is one of two small basic regulatory protein in HIV. Binding of Rev to the Rev-response element RNA (RRE) results in a change in the ratio of spliced and unspliced viral mRNAs that appear in the cytoplasm. Formation of this interaction is a key point in the replication cycle of HIV. We have recently completed the structure determination of the wild-type RNA-peptide complex. Structure calculations reveal that an alpha-helical peptide is inserted into the major groove of the RNA, which adopts an unusual structure due to the presence to two purine-purine base pairs. The present effort lies in characterizing the complex between a mutant Rev peptide that was selected for complementation of a point mutant in the RRE. The affinity of the double mutant complex is nearly the same as the wild-type complex, but the affinity of the wild-type peptide for the mutant RNA and vice versa are reduced. We seek to understand the structural changes that lie at the heart of this specificity switch.